Quality Control of Stem Cell-Based Cultured Meat According to Specific Differentiation Abilities.

The demand for stem cell-based cultured meat as an alternative protein source is increasing in response to global food scarcity. However, the definition of quality controls, including appropriate growth factors and cell characteristics, remains incomplete. Cluster of differentiation (CD) 29 is ubiquitously expressed in bovine muscle tissue and is a marker of progenitor cells in cultured meat. However, CD29+ cells are naturally heterogeneous, and this quality control issue must be resolved. In this study, the aim was to identify the subpopulation of the CD29+ cell population with potential utility in cultured meat production. The CD29+ cell population exhibited heterogeneity, discernible through the CD44 and CD344 markers. CD29+CD44-CD344- cells displayed the ability for long-term culture, demonstrating high adipogenic potential and substantial lipid droplet accumulation, even within 3D cultures. Conversely, CD29+CD44+ cells exhibited rapid proliferation but were not viable for prolonged culture. Using cells suitable for adipocyte and muscle differentiation, we successfully designed meat buds, especially those rich in fat. Collectively, the identification and comprehension of distinct cell populations within bovine tissues contribute to quality control predictions in meat production. They also aid in establishing a stable and reliable cultured meat production technique.

Does a cervical pessary reduce the rate of preterm birth in women with a short cervix?

OBJECTIVES: To evaluate neonatal outcomes after the use of a cervical pessary in Japanese women with short cervical length (CL) less than 25 mm. METHODS: This multicenter study involved women with singleton pregnancies between 20 and 29+6 gestational weeks and a CL of less than 25 mm. The primary outcome was preterm birth (PTB) before 34 weeks of gestation. This study was registered in the Japan Registry of Clinical Trials (JRCT: jRCTs042180102). RESULTS: Two hundred pregnant women were enrolled; 114 in the pessary group and 86 in the expectant management group as controls. In the pessary group, all 114 neonates were investigated for perinatal outcomes, and 112 pregnant women were investigated for primary, and secondary outcomes. In the control group, 86 pregnant women were investigated for primary and secondary outcomes and 86 neonates were investigated for neonatal outcomes. There were no significant differences in PTB in ≤34, ≤37, and ≤28 weeks of gestation or in preterm rupture of membranes (PROM) ≤34 weeks between the groups. The gestational weeks at birth and birth weight were significantly higher in the pessary group. Regression analysis demonstrated that the CL decreased without a pessary, whereas the shortening rate was suppressed during the intervention. No significant differences were observed in adverse neonatal outcomes, chorioamnionitis, or preterm PROM. CONCLUSIONS: The cervical pessary effectively reduced CL shortening during pregnancy resulting in an average increased gestational age, however, did not reduced the rates of preterm birth.

Trends of fetal chromosome analysis by amniocentesis before and after beginning of noninvasive prenatal testing: A single-center experience in Japan.

AIM: This study is to investigate the role of amniocentesis for prenatal diagnosis before and after the beginning of noninvasive prenatal testing (NIPT) in Japan. METHODS: We performed a retrospective analysis of genetic amniocentesis at mid-trimester (15-20 gestational weeks) for fetal karyotype analysis at Nagoya City University between April 2006 and March 2020. The indications, test results, and the detection rate of fetal abnormal karyotype were compared before (phase 1, P1) and after (phase 2, P2) beginning of NIPT at April 2013. RESULTS: A total of 2458 (P1: 1132, P2: 1326) amniocentesis were enrolled in this study. The most frequent indication was advanced maternal age in both phases (P1: 78.2% %, P2: 81.1%). In P2, 110 patients (8.3%) received amniocentesis after positive or nonreportable NIPT results. Other indications were fetal abnormal findings by ultrasounds (P1: 15.4%, P2: 17.7%), abnormal maternal serum screening results (P1: 8.0%, P2: 10%), previous child with fetal chromosome aberration (P1: 6.5%, P2: 3.5%), and translocation of either partner (P1:1.5%, P2: 2.1%). The detection rate for fetal chromosomal aberrations including all indications was significantly increased in P2 (15.9%, 95% CI 14.0-18.0) as compared to P1 (9.0%, 7.4-10.8). However, if the indication was only advanced maternal age, the positive detection rate kept low in both phases (P1: 5.2%, 3.7-7.1, P2: 4.2%, 2.9-5.9). CONCLUSION: Since the initiation of NIPT, the detection rate of fetal chromosomal abnormalities was higher in this study, suggesting that amniocentesis cannot be strongly recommended for advanced maternal age alone.

Study of Relationship Between Mode of Conception and Non-Specific Psychological Distress in Women Undergoing Noninvasive Prenatal Testing.

BACKGROUND: Noninvasive prenatal testing (NIPT) has been performed worldwide to detect common fetal chromosomal aneuploidies. METHODS: Pregnant women (n=3743) with advanced maternal age who visited Nagoya University for NIPT were enrolled in this study. The K6 mental stress scores, that is non-specific psychological distress scores were obtained by questionnaires which were administered pre-NIPT and postpartum. High K6 scores (≥10) indicate anxiety or depression. The K6 stress scores at pre-NIPT and postpartum were evaluated about the relationship between mode of conception and non-specific psychological distress using binomial logistic regression. RESULTS: In general, 7.5% of pre-NIPT women (179/2393) and 5.1% of postpartum women (121/n) were found with high K6 scores. They also did not differ significantly based on maternal age, previous live birth, previous miscarriage, and mode of conception, i.e., natural conception, artificial insemination with husband (AIH), or assisted reproductive technology (ART). Moreover, the prenatal K6 scores were not significantly higher than those at postpartum. CONCLUSION: Our present data suggest that mental distress in women undergoing NIPT during pregnancy and after birth has no statistical relationship with maternal age, previous live birth, previous miscarriage, or infertility treatment, and continuous mental care may help reduce mental distress in the postpartum period.

Performance and outcomes of noninvasive prenatal testing for twin pregnancies in Japan.

AIM: The purpose of this study was to describe the characteristics of women with twin pregnancies who undergo noninvasive prenatal testing (NIPT) as well as the post-partum and neonatal outcomes of such cases in Japan. METHODS: The study population consisted of women who were pregnant with twins and who underwent NIPT using massively parallel sequencing (MPS) at Nagoya City University Hospital between April 2013 and June 2016. Questionnaires were completed pre-NIPT and post-partum. RESULTS: Among 4009 women who underwent NIPT during the study period, 75 women (1.9%) were pregnant with twins. Fifteen women (20%) experienced vanishing twin/intrauterine fetal deaths at <22 weeks, and 60 women (80%) had normal twin pregnancies at the time of genetic counseling for NIPT. The use of NIPT was correlated with increased proportions of women using assisted reproductive technology (ART). The test had a high performance, with a false-positive rate of 1.7% and no false negatives. CONCLUSION: In this study, NIPT had a high performance, with a false positive rate of 1.7% and no false negatives. When treating women with twin pregnancies, the efficacy of NIPT should be explained during genetic counseling. Further larger studies are required to assess the reliability and validity of NIPT in twin pregnancies.

Association of retinal vessel calibers and longitudinal changes in arterial stiffness: the Nagahama study.

OBJECTIVE: Morphological change in retinal vessel calibers has been reported as a marker of cardiovascular risk, but its association with arterial stiffening, a possible factor relating retinal vessel sings and cardiovascular outcomes, is not clear. The study aim was to clarify the relationship between retinal small vessel calibers and longitudinal change in large arterial stiffness in a sample of the general population. METHODS: The study included 6720 Japanese participants (52.1 ±â€Š12.8 years). Central retinal arteriolar equivalent (CRAE) and venular equivalent were measured by fundus photography. Arterial stiffness was evaluated by brachial-to-ankle pulse wave velocity (baPWV) at baseline and at 5 years. RESULTS: The overall change in baPWV (ΔbaPWV) during a mean follow-up 1814 ±â€Š136 days was 41 ±â€Š131 cm/s (3.4 ±â€Š9.9%), and was significantly increased in individuals with narrower CRAE (quartiles: Q1, 4.3 ±â€Š10.6%; Q2, 3.3 ±â€Š10.0%; Q3, 3.1 ±â€Š9.3%; Q4, 3.1 ±â€Š9.7%, P = 0.001). No significant association was observed with central retinal venular equivalent. Multivariate analysis identified CRAE as a significant inverse determinant of ΔbaPWV (ß = -0.033, P = 0.006) independent of possible covariates including age, sex, blood pressure, and baseline baPWV. The association between CRAE and ΔbaPWV was prominent in a middle-aged (age Q2, ß = -0.078, P = 0.002), but not younger (Q1, P = 0.232) or older (Q3, P = 0.427; Q4, P = 0.542) participants. CONCLUSION: Narrower CRAE in middle-age was associated with the long-term risk of arteriosclerosis in a general population sample.

Psychological distress in post-partum women after non-invasive prenatal testing (NIPT) in Japan.

AIM: The purpose of this study was to clarify the characteristics of psychological mental distress in post-partum women after non-invasive prenatal testing (NIPT) in Japan. METHODS: Psychological mental distress was assessed using the Kessler Psychological Distress Scale (K6). We compared patients with (i) low pre-NIPT K6 and low post-partum K6 scores (control group), and (ii) low pre-NIPT K6 and a high post-partum K6 scores (case group). RESULTS: Among the 697 women who underwent NIPT, 29 (4.2%) had low pre-NIPT K6 and high post-partum K6 scores (case group) and 668 (95.8%) had low pre-NIPT K6 and low post-partum K6 scores (control). Among women with negative NIPT findings, post-partum women with a high K6 score were compared to a control group of women with a low K6 score. Logistic regression analysis showed that primiparity (P = 0.007), low birthweight (P = 0.005) and use of intracytoplasmic sperm injection (P = 0.02) and assisted reproductive technology (P = 0.05) were significantly different between the groups. CONCLUSION: Even if women do not feel mental distress before NIPT, they may develop mental stress post-partum. In particular, primipara women who conceived through assisted reproductive technology (especially intracytoplasmic sperm injection) and gave birth to a low birthweight baby were more susceptible to developing post-partum distress. Thus, it is important to educate women that support is available, with consultation with other healthcare professionals during genetic counseling if necessary. Further studies are needed in order to determine the factors associated with post-partum mental distress.

A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.

Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10-5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10-9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10-7 and 9.73 × 10-7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.

Background of couples undergoing non-invasive prenatal testing in Japan.

AIM: Our purpose was to assess the background of couples who were undergoing non-invasive prenatal testing (NIPT) in Japan. METHODS: The characteristics of 2486 women who had visited Nagoya City University Hospital for NIPT were compared with Japanese Demographic Trends as controls. The questionnaire included items regarding the maternal and paternal age, maternal age at marriage, age at first live birth, and conception mode. RESULTS: Compared with the controls, the percentage of women who were 4 or more years older than their partners was larger in the NIPT group (11.8% vs 6.5%). The maternal age at marriage, age at first live birth, and the duration between marriage and first birth tended to be greater in the NIPT group (32.6 years vs 29.3 years, 36.9 years vs 30.4 years, and 3.6 years vs 2.4 years, respectively), and the percentage of women who underwent assisted reproductive technology tended to be higher in the NIPT group (35-39 years: 21.2% vs 7.5%, 40-45 years: 36.2% vs 12.6%), compared with the controls. CONCLUSION: Knowing the specific backgrounds of couples who have undergone NIPT may be important for improving the quality of genetic counseling for NIPT.

MMP20 and ARMS2/HTRA1 Are Associated with Neovascular Lesion Size in Age-Related Macular Degeneration.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe visual impairment. Despite treatment, a central scotoma often remains. The size of the scotoma depends on the lesion size of the choroidal neovascular membrane and significantly affects the patient's quality of life, and the lesion size of neovascularization also affects response to treatments. The aim of this study was to identify genes associated with the neovascular lesion size in neovascular AMD. DESIGN: A genome-wide association study (GWAS). PARTICIPANTS: We included 1146 Japanese patients with neovascular AMD. METHODS: We performed a 2-stage GWAS for the lesion size of AMD as a quantitative trait among 1146 (first stage: 727, second stage: 419) Japanese patients with neovascular AMD. Lesion size was determined by the greatest linear dimension measured with fluorescein angiography examination before treatment. We examined the association between the genotypic distribution of each single nucleotide polymorphism (SNP) and the trait using an additive model adjusted for age and sex. To evaluate the associations between AMD development and SNPs associated with lesion size, we also performed a case-control study by using the genotype data from these 1146 Japanese patients as case subjects and the fixed dataset from the Nagahama Study as control subjects. MAIN OUTCOME MEASURES: Genes associated with the lesion size in neovascular AMD. RESULTS: In the discovery stage, rs10895322 in MMP20 showed a genome-wide significant P value of 6.95×10(-8), and rs2284665 in ARMS2/HTRA1 showed a P value of 1.55×10(-7). The associations of these 2 SNPs were successfully replicated in the replication stage, and a meta-analysis of both stages showed genome-wide significant P values (2.80×10(-9) and 4.41×10(-9), respectively). In a case-control study using 3248 Japanese subjects as controls, we could not find contribution of MMP20 rs10895322 for AMD development. Although MMP20 has been thought to be expressed only in dental tissues, we confirmed MMP20 expression in the human retina and retinal pigment epithelium/choroid with polymerase chain reaction. CONCLUSIONS: The growth of choroidal neovascularization in AMD would be affected by 2 genes: MMP20, a newly confirmed gene expressed in the retina, and ARMS2/HTRA1, a well-known susceptibility gene for AMD.

Descriptive epidemiology of spot urine sodium-to-potassium ratio clarified close relationship with blood pressure level: the Nagahama study.

OBJECTIVES: We undertook descriptive epidemiology of spot urine sodium-to-potassium ratio (Na/K) in a population sample to clarify the close relationship between Na/K and blood pressure level independently of potential confounding factors. METHODS: Study participants consisted of 9144 apparently healthy citizens (aged 54 ±â€Š13 years). All clinical parameters were obtained at baseline. RESULTS: Na/K was significantly higher in hypertensive individuals irrespective of antihypertensive medication status (normotension, 3.12 ±â€Š1.82; untreated hypertension 3.50 ±â€Š1.96; treated hypertension, 3.72 ±â€Š2.53). As urinary Na (ß = 0.092, P < 0.001) and K (ß = -0.050, P < 0.001) levels were inversely associated with BP, Na/K (ß = 0.118, P < 0.001) was more closely associated with BP than Na or K alone, as well as daily salt intake estimated from urinary Na (ß = 0.088, P < 0.001). Several factors were significantly associated with Na/K, namely age, sex, obesity, blood pressure, renal function, salt restriction status, serum phosphate and urinary creatinine level, and fasting period and season at urine sample collection. However, the association between Na/K and BP was independent of these factors (adjusted ß = 0.112, P < 0.001). No direct association was observed between Na/K and large arterial remodeling assessed by pulse wave analysis (P = 0.496) or retinal arteriolar morphological change (P = 0.431). Further, a genome-wide association study failed to identify any particular genotype influencing urinary Na and K levels. CONCLUSIONS: Although we clarified several factors that might affect spot urine Na/K, these relationships were not substantial enough to confound the association between urinary Na/K and BP. A simple measure of Na/K might be more representative of salt loading obtained from spot urine samples than Na excretion alone.

The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye.

PURPOSE: To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye. METHODS: This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated. RESULTS: The ARMS2 rs10490924 recessive model (hazard ratio [HR]meta = 2.04; Pmeta = 3.4 × 10⁻³) and CFH rs800292 additive model (HRmeta = 1.77; Pmeta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I² = 0%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 × 10⁻5; I² = 0%). After 10 years from the first visit, the patients within the top 10% by GRS showed a 51% hazard rate, in contrast to 2.3% among patients within the lowest 10% by GRS. CONCLUSIONS: We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD.

Sensitivity and specificity for detecting early glaucoma in eyes with high myopia from normative database of macular ganglion cell complex thickness obtained from normal non-myopic or highly myopic Asian eyes.

PURPOSE: We aimed to determine the sensitivity and specificity of the normative database of non-myopic and highly myopic eyes of the macular ganglion cell complex (mGCC) thickness embedded in the NIDEK RS-3000 spectral-domain optical coherence tomography (SD-OCT) for detecting early glaucoma in highly myopic eyes. METHODS: Forty-seven highly myopic eyes (axial length ≥26.0 mm) of 47 subjects were studied. The SD-OCT images were used to determine the mGCC thickness within a 9-mm diameter circle centered on the fovea. The sensitivity and specificity of the non-myopic database were compared to that of the highly myopic database for distinguishing the early glaucomatous eyes from the non-glaucomatous eyes. The mGCC scans were classified as abnormal if at least one of the eight sectors of the significance map was < 1 % of the normative thickness. RESULTS: Twenty-one eyes were diagnosed to be non-glaucomatous and 26 eyes to have early glaucoma. . The average mGCC thickness was significantly thinner (80.9 ± 8.5 µm) in the early glaucoma group than in the non-glaucomatous group (91.2 ± 7.5 µm; p <1 × 10(-4)). The sensitivity was 96.2 % and specificity was 47.6 % when the non-myopic database was used, and the sensitivity was 92.3 % and the specificity was 90.5 % when the highly myopic database was used. The difference in the specificity was significant (p < 0.01). CONCLUSIONS: The significantly higher specificity of the myopic normative database for detecting early glaucoma in highly myopic eyes will lead to fewer false positive diagnoses. The database obtained from highly myopic eyes should be used when evaluating the mGCC thickness of highly myopic eyes.

Parental decisions following prenatal diagnosis of chromosomal abnormalities: implications for genetic counseling practice in Japan.

Parental decision-making to terminate or continue a pregnancy was studied after prenatal diagnosis of a chromosome aneuploidy among a sample of patients around the city of Nagoya, Japan. A total of 1,051 amniocentesis cases at 15-18 weeks of gestation were analyzed. Of these, 60 cases of chromosomal anomalies with aneuploidies were diagnosed by conventional cytogenetic analysis. Of the 45 diagnoses of autosomal chromosome aneuploidies, pregnancy was terminated in 93.3 % of the cases. Of the 15 cases diagnosed with sex chromosome aneuploidy, pregnancy was terminated in 46.7 %. Differences in parental decisions with respect to maternal age, gestational week at diagnosis, number of pregnancies per individual and existing number of children were not significant in patients diagnosed either with autosomal or sex chromosome aneuploidy. The findings indicate that when diagnosed with a chromosome aneuploidy in which a severe prognosis was expected, most couples decided to terminate the pregnancy in Japan. Implications of these findings for expanding the profession of genetic counseling are discussed and research recommendations are provided.

Central blood pressure relates more strongly to retinal arteriolar narrowing than brachial blood pressure: the Nagahama Study.

OBJECTIVES: Although central blood pressure (BP) is considered to be more closely associated with large arterial remodeling and cardiovascular outcomes than brachial BP, few studies have investigated these associations with changes in small arteries. As morphological changes in retinal vessels might be associated with cardiovascular outcomes, we conducted a cross-sectional study to investigate the association of central BP with retinal vessel caliber. METHODS: The study included 8054 Japanese participants. Central BP was estimated by the radial arterial waveform by calibrating brachial BP. Central retinal arteriolar equivalent (CRAE) was computationally measured using fundus photography. RESULTS: CRAE was most strongly associated with central SBP (r = -0.324, P < 0.001), followed by DBP (r = -0.292, P < 0.001) and central pulse pressure (PP; r = -0.226, P < 0.001). The correlation coefficient between SBP and CRAE was significantly greater in central SBP than in brachial SBP (r = -0.300, P < 0.001). After adjustment for possible covariates, brachial SBP (ß = -0.221, P < 0.001) and central SBP (ß = -0.239, P < 0.001) were independently associated with CRAE. Further, higher brachial SBP (ß = -0.226, P < 0.001) and smaller PP amplification (ß = 0.092, P < 0.001) were identified as independent determinants of narrowing of CRAE in the same equation, which indicated the superiority of central BP. Central BP-determined hypertensive individuals had a significantly narrower CRAE independent of brachial BP (central/brachial: hypertension/hypertension 121.4 ±â€Š11.5, hypertension/normotension 120.9 ±â€Š11.2, normotension/hypertension 125.1 ±â€Š11.9, normotension/normotension 128.1 ±â€Š11.5 µm). CONCLUSION: Central BP was more closely associated with the narrowing of CRAE than brachial BP. Slight increases in central BP might be involved in the morphological changes in small retinal arteries, even in individuals with optimal brachial BP.

Comprehensive replication of the relationship between myopia-related genes and refractive errors in a large Japanese cohort.

PURPOSE: We investigated the association between refractive error in a Japanese population and myopia-related genes identified in two recent large-scale genome-wide association studies. METHODS: Single-nucleotide polymorphisms (SNPs) in 51 genes that were reported by the Consortium for Refractive Error and Myopia and/or the 23andMe database were genotyped in 3712 healthy Japanese volunteers from the Nagahama Study using HumanHap610K Quad, HumanOmni2.5M, and/or HumanExome Arrays. To evaluate the association between refractive error and recently identified myopia-related genes, we used three approaches to perform quantitative trait locus analyses of mean refractive error in both eyes of the participants: per-SNP, gene-based top-SNP, and gene-based all-SNP analyses. Association plots of successfully replicated genes also were investigated. RESULTS: In our per-SNP analysis, eight myopia gene associations were replicated successfully: GJD2, RASGRF1, BICC1, KCNQ5, CD55, CYP26A1, LRRC4C, and B4GALNT2.Seven additional gene associations were replicated in our gene-based analyses: GRIA4, BMP2, QKI, BMP4, SFRP1, SH3GL2, and EHBP1L1. The signal strength of the reported SNPs and their tagging SNPs increased after considering different linkage disequilibrium patterns across ethnicities. Although two previous studies suggested strong associations between PRSS56, LAMA2, TOX, and RDH5 and myopia, we could not replicate these results. CONCLUSIONS: Our results confirmed the significance of the myopia-related genes reported previously and suggested that gene-based replication analyses are more effective than per-SNP analyses. Our comparison with two previous studies suggested that BMP3 SNPs cause myopia primarily in Caucasian populations, while they may exhibit protective effects in Asian populations.

Association of focal choroidal excavation with age-related macular degeneration.

PURPOSE: To study the prevalence, tomographic features, and clinical characteristics of focal choroidal excavation (FCE) in eyes with exudative age-related macular degeneration (AMD). METHODS: We examined 243 consecutive eyes with exudative AMD with a prototype swept-source optical coherence tomography (OCT) system. Three-dimensional images of the macular area, covering 6 × 6 mm(2), were reconstructed by segmentation of the outer surface of the retinal pigment epithelium. RESULTS: Three-dimensional swept-source OCT revealed 15 excavations in 12 eyes (4.9%); 10 had a single excavation and 2 had multiple excavations (2 and 3 excavations, respectively). In multiaveraged scans, unusual choroidal tissue was found beneath 5 excavations, bridging the excavation with the outer choroidal boundary. Additionally, the suprachoroidal space was observed beneath 7 excavations-the outer choroidal boundary appeared to be pulled inward by this bridging tissue. In 9 excavations, color fundus photographs showed pigmentary disturbance. Fourteen excavations (93.3%) were located within or adjacent to the choroidal neovascularization area. Compared with eyes without FCE, in eyes with FCE, the mean age was significantly higher (P = 0.040) and mean visual acuity was significantly better (P = 0.014). In addition, polypoidal lesions were observed in 8 of 12 eyes with FCE, but they appeared to have a limited effect on either the rate of FCE (P = 0.44) or the clinical characteristics of the eyes. CONCLUSIONS: While FCE may be partially related to the choroidal neovascularization associated with exudative AMD, other factors may also influence this association.

Non-specific psychological distress in women undergoing noninvasive prenatal testing because of advanced maternal age.

OBJECTIVE: The objective of our study was to describe our clinical experience in providing noninvasive prenatal testing (NIPT) for fetal aneuploidy to pregnant women, highlighting the degree of non-specific psychological distress. METHODS: Data were collected from Japanese women who were offered and underwent NIPT after genetic counseling and control pregnant women who did not undergo NIPT as part of the Japan Environment and Children's Study Control A planning. The degree of mental distress was assessed using the Kessler 6 (K6) screening scale with a score of ≥10 indicating depression or anxiety disorder. RESULTS: Among the 505 women who underwent NIPT because of advanced maternal age, 9.1% had a K6 score of ≥10. Compared with matched controls (n = 1010) adjusted for maternal age and gestational age, the NIPT group showed a trend toward higher K6 scores (odds ratio 1.44, 95% confidence interval 0.97-2.13, P = 0.07). Higher K6 scores were associated with women whose husbands were the primary decision makers during NIPT counseling (P = 0.06). CONCLUSIONS: Women electing NIPT tend to have higher scores of depression/anxiety, and those with higher depression scores tended to defer the decision to their husbands.